The human retrovirus human T-cell leukemia/lymphotropIc virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In contrast to human immunodeficiency virus type I infection, only a small percentage of those infected with HTLV-I will develop disease. Such differences in the manifestations of infection could be related to viral-specific factors, host factors or both. The goal of these studies is to further understand viral-specific factors that might determine disease pathogenesis during HTLV-I infection. We, as well as others, have now reported on the existence of newly recognized alternatively spliced viral messenger ribonucleic acids (RNA) from the pX region of HTLV-I. Regulation of the expression of these alternatively spliced messages and/or expression of proteins encoded by these regions may influence the outcome of infection in the host. RNase protection analysis of total RNA from cell lines established from patients with ATL and TSP/HAM using specific RNA probes from the newly mapped spliced junctions confirmed the existence of these alternatively spliced messages and indicated that they could be found during infection established from viral strains of different pathogenic origin. The function of p2I(rex) protein of HTLV-I has remained elusive despite a number of in vitro studies; therefore, we have used the transgenic mouse model to further study this protein. We have established transgenic murine lines that have the transgene p2I(rex) under the cytomegalovirus promoter. Founder lines have been established followed by successful breeding of heterozygous and homozygous mice in the F2 generation. Some of these mice exhibit wasting and neurologic signs, indicating that expression of this protein may be associated with a phenotype that could have relevance to the function of this gene in HTLV-I disease. Analysis of these mice should give important insight into the function and pathologic effects of this viral gene product.